tbuckley/cabot-search huggingface dataset:
Impact of homelessness on outcomes among pancreatic cancer hospitalization: Insight from the 2016-2020 National Inpatient Sample.
Authors: Alekhya Pagidipally, Shivani Sharma, Mehndi Dandwani, Suma Sri Chennapragada, Kamleshun Ramphul, Renuka Verma, Sailaja Sanikommu, Shaheen Sombans, Stephanie G Mejias, Balkiranjit Kaur Dhillon, Petras Lohana, Fnu Arti, Vijay Kumar
Journal: Journal of Clinical Oncology (2023)

e16264 Background: Homelessness is a major socio-economic issue in the United States, affecting an estimated 171 per 100,000 persons in certain states. While pancreatic cancer (PC) tends to have a poor prognosis, the disease requires an early diagnosis, proper care, and follow-ups. As there is a paucity of data highlighting differences in patient characteristics and outcomes of homeless patients with PC, a retrospective study was conducted via a national database. Methods: We used data from the 2016-2020 National Inpatient Sample (NIS), the most extensive hospital database, to identify patients with a diagnosis of pancreatic cancer. Patients with a status of “homeless” were located via the ICD-10 code “Z590”, per suggestions from HCUP and past studies. Several differences in patient characteristics were explored between homeless cases of PC and non-homeless cases via Pearson’s Chi-Square tests. Finally, the adjusted odds ratio (aOR) and 95% Confidence intervals (CI) of various outcomes such as mortality, pulmonary embolism, septicemia, and hepatic failure were calculated via multivariable logistic regression models. Results: Our study identified 544855 pancreatic cancer cases, including 1380 patients classified as homeless (0.3%). 81.5% of homeless patients were males (vs. 52.1%), and 24.6% were admitted on weekends (vs. 20.6%). Moreover, Medicaid was the prime insurer among homeless patients (47.6% vs. 8.6%) with a higher mean hospital charge ($86796 vs. $70610). Racial differences were also observed as 51.9% of homeless cases were Whites (vs. 71.2%), while 31.6% (vs. 13.8%) were Blacks, and 11.3% (vs. 8.2%) were Hispanics. A higher proportion of homeless cases had palliative care utilization (27.9% vs. 19.1%), a Do-Not-Resuscitate (DNR) order (25.7% vs. 23.1%), and required pancreatic and proximal biliary dilation/stenting (4.0% vs. 2.2%). Homeless patients admitted with pancreatic cancer also expressed higher odds of in-hospital mortality (8.7% vs. 7.4%, aOR 1.625, 95% CI 1.280-2.064, p&lt;0.01). No statistical significance was found for events of pulmonary embolism (aOR 1.231, p=0.160), septicemia (aOR 1.044, p=0.674), and hepatic failure (aOR 0.892, p=0.549). Conclusions: Homeless patients with PC were linked with higher in-patient mortality. Various racial and socio-economic differences were also observed. Several efforts to ameliorate access to care among homeless patients and an early diagnosis may help improve the outcomes.
Outcomes among survivors of childhood cancer in low- and middle-income countries: A systematic review.
Authors: Avram Denburg, Kevin Alexander Wong, Alexandra Moskalewicz, Sumit Gupta
Journal: Journal of Clinical Oncology (2023)

10057 Background: Low- and middle-income countries (LMICs) account for most of the global childhood cancer burden. Though cure rates lag behind those in high-income countries (HICs), a substantial proportion of LMIC children do survive. Long-term side effects of cancer or cancer therapy (late effects) are well-documented among childhood cancer survivors (CCS) in HICs, but whether prevalence and risk factors of late effects are comparable in LMICs is unclear. We thus conducted a systematic review to assess LMIC CCS outcomes. Methods: Five major health sciences databases were searched from inception to November 2022 in all languages. We included observational studies conducted in LMICs (World Bank 2021 classification) that evaluated outcomes in CCSs diagnosed with any malignancy. Mean or median length of follow-up must have been ≥ 5 years from original cancer diagnosis. Meta-analyses were precluded by cohort and outcome heterogeneity. Results: Of 1,994 studies identified, 113 underwent full-text review and 21 met inclusion criteria (16 full articles and 5 conference abstracts). Studies were conducted in lower-middle income (N = 12, 57%) or upper-middle income (N = 9, 43%) countries; no low-income country data were found. Study regions were mainly South and East Asia (N = 10, 48%) and the Americas (N = 8, 38%). Almost half (N = 9, 43%) of studies were conducted in India and only one African study from Cameroon was identified. Over half (N = 12, 57%) of studies were cross-sectional in design. Only five (24%) cohorts were comprised entirely of 5-year survivors. CCS of all childhood cancer types were evaluated in 12 (57%) cohorts, and 9 (43%) were specific to one cancer type. Ten (48%) studies were conducted in a survivorship clinic. Second cancers, followed by endocrine, reproductive, and cardiovascular late effects were most frequently assessed. Second cancers were reported in 1%–11% of CCS cohorts (N = 10 studies). The prevalence of hypothyroidism and metabolic syndrome ranged from 2%-49% (N = 6 studies) and 4%-17% (N = 5 studies), respectively. Gonadal dysfunction ranged from 2%-82% (N = 6 studies). Cardiac dysfunction and hypertension ranged from 1%-16% (N = 3 studies) and 5-19% (N = 3 studies), respectively. Late effects of the musculoskeletal (N = 4 studies) and urinary (N = 4 studies) systems were least investigated. Conclusions: Substantial knowledge gaps exist in LMIC childhood cancer survivorship. Few LMIC-based studies were identified, with no low-income country data available. In middle-income countries, variability existed in how late effects were defined and assessed; data was also limited by selection bias and small sample sizes. Additional systematically collected data on LMIC CCS cohorts are urgently needed.
Partial tumor irradiation plus pembrolizumab in treating large advanced solid tumor metastases.
Authors: Mark Charles Korpics, Benjamin Ernst Onderdonk, Rebekah E Dadey, Jared H Hara, Lilit Karapetyan, Yuanyuan Zha, Theodore Karrison, Adam C. Olson, Gini F. Fleming, Ralph R. Weichselbaum, Riyue Bao, Steven J. Chmura, Jason J. Luke
Journal: Journal of Clinical Oncology (2023)

2593 Background: We previously demonstrated the safety of stereotactic body radiotherapy followed by pembrolizumab (SBRT+P) in patients with advanced solid tumors. This phase 1 clinical trial was expanded to study the safety of partial tumor irradiation (partial-Rx). We assessed irradiated local failure (LF) and clinical outcomes with correlations to biomarkers including CD8-T-cell radiomics score (RS) and circulating cytokines. Methods: Patients received SBRT to 2-4 metastases and pembrolizumab ≤7 days after SBRT. Tumors &lt;65cc received the full radiation dose (complete-Rx), whereas tumors &gt; 65cc received partial-Rx. Landmark analysis was used to assess the relationship between tumor response and overall survival (OS). Multivariable analysis was performed for RS and circulating cytokines. Results: In the combined (expansion plus original) cohort, 97 patients (219 metastases) were analyzed and received SBRT+P. Forty-six (47%) patients received &gt;1 partial-Rx treatment. There were 7 (7.2%) dose-limiting toxicities (DLTs). 1-year LF was 7.6% overall, and 13.3% and 5.4% for partial-Rx and complete-Rx tumors, respectively (hazard ratio 2.32, 95% confidence interval: 0.90-5.97, p = 0.08). The overall, unirradiated, and irradiated objective response rate was 22%, 12%, and 34%, respectively. Irradiated tumor response to SBRT+P was associated with prolonged OS; 1-year OS was 71% (responders), 42% (mixed-responders), and 0% (non-responders) (p &lt; 0.01). High-RS was significantly associated with improved LF, progression-free survival (PFS), and OS. Elevated circulating IL-8 was independently associated with inferior PFS and OS. Conclusions: SBRT+P is safe in patients with large, advanced solid tumors. Additional studies are warranted to assess non-inferiority of complete versus partial irradiation of tumors in the setting of immunotherapy. Clinical trial information: NCT02608385 .
Patient access to precision medicine: Identifying barriers to biomarker testing in non-small cell lung cancer.
Authors: Ayse Levent, Pieter De Richter, Hope Bender
Journal: Journal of Clinical Oncology (2023)

3131 Background: The growing number of targeted therapies approved to treat non-small cell lung cancer (NSCLC) has anchored biomarker testing in clinical practice. Despite general concordance across international guidelines recommending advanced NSCLC patients be tested for oncogenic alterations and immune biomarkers, this is not always the case. This study uses real-world data to explore the barriers to testing across US, Japan, Germany and China. Methods: Ipsos’ Biomarker Testing Rate Monitor is a multi-stakeholder, physician-reported syndicated patient record database. 206 cancer-treating physicians (US=69, Japan=37, Germany=41, China=59) were screened for seniority and caseload and submitted data on 990 NSCLC patients (aggregate) in which biomarker testing had not taken place. Data were collected online January – December 2022. Results: Analyzing physician cited barriers why patients were not tested, choosing not to test at patient’s current stage was highest in the reported US patient cohort, guidelines not calling for testing at this point was more frequently cited in the Japan (27%) and Germany (25%) patient cohort and patient’s co-pay was more frequently cited in the China cohort (34%). The Japan cohort had higher mentions of tissue not being available. Country disparities in the reported metastatic (IIIB-IV) cohort included lack of tissue in Japan (48%) and Germany (25%), deferring testing to a later point in the US (21%) and high co-pay in China (50%). The top cited reasons are shown. Conclusions: Results from this study indicate that, despite guidelines, not all oncology patients receive biomarker testing. While reimbursement structures are difficult to overcome, a concerted effort is needed to raise awareness of the clinical utility of biomarker testing and of the importance of collecting sufficient tissue during the biopsy to allow patients the chance of benefiting from precision medicines. Similarly, calls for earlier testing would support efforts that ensure the best available treatment options are available to patients throughout their journey. Further investigation using comparator cohort is warranted. [Table: see text]
Analysis of systemic immune changes in patients with advanced cancer treated with immunotoxin LMB-100 and tofacitinib.
Authors: Nebojsa Skorupan, Cody J. Peer, Yunkai Yu, Min-Jung Lee, Sunmin Lee, Shraddha Rastogi, Nahoko Sato, Hyoyoung Choo-Wosoba, Raffit Hassan, William Douglas Figg, Liang Cao, Jane B. Trepel, Ira Pastan, David J.P. FitzGerald, Christine Alewine
Journal: Journal of Clinical Oncology (2023)

e15017 Background: LMB-100 recombinant immunotoxin delivers a modified Pseudomonas exotoxin A payload to mesothelin-expressing tumors. Almost all patients receiving LMB-100 develop anti-drug antibodies (ADAs) after 2 cycles/ 6 doses of the drug, therefore reducing peak serum drug concentrations to near the lower limit of detection. Tofacitinib is an oral JAK inhibitor that had been shown to prevent ADA formation in pre-clinical studies. Apart from assessing safety and tolerability, this trial sought to determine whether co-administration of tofacitinib with LMB-100 delays the formation of neutralizing ADAs so more patients could achieve the peak LMB-100 concentration of &gt; 600 ng/mL during treatment cycle 2. Correlative data examining circulating immune cell subsets and cytokines pre- and on-treatment are presented here. Methods: Patients with pancreatic adenocarcinoma (n = 13) and other mesothelin-expressing solid tumors (n = 3; cholangiocarcinoma, appendix, cystadenocarcinoma) were treated for up to 3 cycles (21 days) with LMB-100 given on days 4, 6, and 8 at 2 dose levels (100 and 140 mcg/kg), accompanied by oral tofacitinib for the first 10 days of the cycle (10 mg BID). Adverse events were assessed as per CTCAE 5.0. Analysis of the cytokine data was performed using a Wilcoxon signed-rank test. Results: DLTs of grade 3 cardiac toxicity (n = 1) and grade 4 hyponatremia (n = 1) were seen at the 140mcg/kg dose of LMB-100. One patient treated at 100 mcg/kg developed a grade 4 pericardial effusion, resulting in early closure of the study for safety. The two patients who experienced cardiac toxicity had lower baseline CD4+ cells and increased CD19+ cells post-LMB-100 treatment. Four out of 8 evaluable patients achieved LMB-100 concentration above the threshold during cycle 2, and 2 out of 3 did so during cycle 3. Analysis of peripheral blood cytokine levels showed sustained increases in TNF-α, IL-8, and IL-10 following LMB-100 administration through to the start of cycle 2. Percentage of Tregs increased through cycle 1 in patients who developed drug-neutralizing ADAs and was significantly higher than in patients with LMB-100 levels above threshold at the start of cycle 2. Conclusions: Combination of LMB-100 with tofacitinib is not safe. An insufficient number of patients was treated to conclusively assess the ability of tofacitinib to stop or delay ADA formation. Increases in circulating Tregs were observed in patients with early neutralizing ADA formation. Clinical trial information: NCT04034238 .
A phase 1, multi-center, open-label, dose-escalation and dose expansion study of CBP-1018, a bi-ligand-drug conjugate, in patients with heavily treated advanced solid tumors.
Authors: Kaiwen Li, Junyan Wu, Suiwen Ye, Yanqiong Liu, Hao Huang, Fan Fan, Yiming Lai, Suili Zhuang, Liyan Zhou, Robert Huang, Yan Teng, Xiaoyan Chai, Yehui Shi, Hai Huang
Journal: Journal of Clinical Oncology (2023)

e15007 Kaiwen Li and Junyan Wu contributed equally to this work. Yehui Shi and Hai Huang are the corresponding authors. Background: Prostate-specific membrane antigen (PSMA) or folate hydrolase 1 (FOLH1) is highly expressed on prostate cancer and folate receptor α (FRα) overexpressed in various malignant tissues which both related to tumor invasiveness. CBP-1018 is a first-in-class bi-ligand-drug conjugate targeting both PSMA and FRα with monomethyl auristatin E (MMAE) as payload. Methods: This phase 1 study included both a dose-escalation and expansion stage. In the dose-escalation stage, an accelerated titration was conducted in single patient at 0.03mg/kg followed by an i3+3 design for dose levels (DLs) ≥ 0.06 mg/kg, Q2W in a 4-week cycle. This stage mainly enrolled patients (pts) with metastatic castration resistant prostate cancer (mCRPC) received a median 3.5 prior lines of treatment. The primary objectives were to evaluate the safety and tolerability, determine dose limiting toxicity (DLT) and maximum tolerated dose (MTD). Additionally, pharmacokinetics (PK) and preliminary efficacy will also be evaluated. Results: As of 24 Nov 2022, 14 pts (12 mCRPC, 1 bladder cancer and 1 ureteral carcinoma) were enrolled at 5 DLs (1 pt at 0.03 mg/kg, 3 pts each at 0.06, 0.08, 0.10 mg/kg, 4 pts at 0.12 mg/kg). No DLTs or drug-related deaths were observed. For 9 pts (64.3%) experienced treatment-related adverse events (TRAEs) ≥ grade 3, most common were neutrophil decrease (35.7%), WBC decrease (28.6%), lymphocyte decrease (14.3%), elevated GGT (14.3%) and hypertriglyceridaemia (14.3%). Among 10 efficacy evaluable pts with mCRPC, 3 SD were observed at DLs of 0.08, 0.10, and 0.12mg/kg, 4 non-PD at 0.06, 0.10, and 0.12 mg/kg, and 3 PD at 0.06 and 0.08 mg/kg. Decrease of prostate-specific antigen (PSA) was detected in 3 pts at 0.10 mg/kg. Overall median PFS was 7.2 months (95%CI, 1.7-9.3) and not reached in mCRPC pts. For PK profile of CBP-1018 and free MMAE, t1/2z was ranged 0.54-1.15 h and 40.28-57.27 h, respectively, no accumulation of both substances after multiple doses. Conclusions: CBP-1018 was well-tolerated at DLs of 0.03-0.12 mg/kg Q2W with no DLTs. Multiple SD were observed at DLs of 0.08-0.12 mg/kg, conferred a promising preliminary antitumor activity in pts with mCRPC. MTD was not reached and dose-escalation to establish the RP2D is continuing. Clinical trial information: NCT04928612 .
Breast malignancy after radioactive iodine ablation for thyroid pathology: A systematic review of the literature.
Authors: Victoria Yellamaty, Yumna Hamid, Daniel N. Efiom-Ekaha
Journal: Journal of Clinical Oncology (2023)

e22511 Background: Radioactive Iodine Ablation (RAI) is a procedure in which the administration of radioactive iodine is utilized to eradicate pathologic thyroid tissue. RAI is commonly used for thyroid malignancy and hyperthyroidism. Although RAI has been a mainstay of treatment for these diseases, there has been some controversy regarding the development of secondary primary malignancy after RAI. Breast cancer is a particular concern. As breast cancer is the second most common cancer for women in the United States, understanding its risk factors is a key component of public health. Methods: A systematic review was conducted following PRISMA guidelines. Inclusion criteria consisted of English language studies that evaluated the association between radioactive iodine ablation and secondary primary breast malignancy. The study was conducted from January 2023 until February 2023. Two independent researchers conducted the literature search utilizing PubMed, SCOPUS, JSTOR, and Wiley Library using standardized search terms. The titles and abstracts of these studies were independently screened, and further evaluated for relevancy. Qualitative data was then extracted and summarized. Results: Of the 386 manuscripts retrieved, 27 met inclusion criteria. These studies were published between 1983 – 2022. Of these, 15 articles reported no association between RAI and the development of secondary primary breast malignancy. Of the manuscripts which reported no association, 6 examined RAI for hyperthyroidism, and 9 examined RAI for thyroid malignancy. 12 studies reported an association between RAI and the development of secondary primary breast malignancy. Of the studies reporting an association, 1 examined RAI for hyperthyroidism, and the remaining 11 examined RAI for thyroid malignancy. For the single study that found an association in the case of hyperthyroidism, the researchers found a dose-dependent relationship. Conclusions: The literature surrounding secondary primary breast malignancy after RAI is controversial. This systematic review resulted in conflicting data regarding the association between radioactive iodine ablation for thyroid pathology and the development of secondary primary breast malignancy. The studies that suggested an association between RAI and secondary primary breast malignancy were overwhelmingly studies in which RAI was used for the treatment of thyroid malignancy. Some studies suggest a possible dose-dependent relationship between RAI and secondary primary breast malignancy, however this data is limited. Additional studies would be beneficial to address this gap in the literature.
Durvalumab and tremelimumab for hepatocellular carcinoma in patients listed for a liver transplant.
Authors: Davendra Sohal, Khaled Fahmy Abouelezz, Katie Moreland, Ralph Quillin, Kristina Lemon, Adam Rojan, Olugbenga Olanrele Olowokure, Ali Kord, Shimul Shah
Journal: Journal of Clinical Oncology (2023)

TPS4188 Background: Hepatocellular carcinoma (HCC) is an aggressive malignancy, developing most often in the setting of liver cirrhosis (Sohal et al Current Oncol Rep 2011; Gordan et al JCO 2020). For advanced disease, immunotherapy has now become standard of care – a combination of atezolizumab and bevacizumab has shown the best overall survival outcome so far (Finn et al NEJM 2020). For earlier stage disease, however, there is no systemic therapy standard. The best treatment for HCC in the setting of cirrhosis is a liver transplant allowing potential cure for both the cancer and cirrhosis. Nonetheless, 25-35% of patients fail to reach liver transplant because of disease progression while waiting for a transplant (Sinha et al, Hepatology 2019) and approximately 15% experience HCC recurrence after transplant (Mehta et al, Transplantation 2020). Taken together, this constitutes a large subset of this patient population who cannot achieve a cure. Given the success of immunotherapy in the advanced setting, it is imperative to study this in the pre-transplant setting, to improve the outcomes cited above. However, there is a theoretical risk of graft rejection with immunostimulatory treatment. Methods: This is a single-arm, open-label, Phase II, multicenter study designed to evaluate the safety and efficacy of durvalumab and tremelimumab for the treatment of HCC patients who have cirrhosis or portal hypertension and are eligible for listing for a liver transplant. Eligibility requirements include adult patients with HCC within UCSF criteria, a Child-Pugh score of up to 7, and ECOG PS of 0 or 1. Treatment includes an immunotherapy combination of 1 dose of tremelimumab and 5 doses of durvalumab for up to 4 months. After a minimum 28-day gap following the final durvalumab dose, patients undergo locoregional therapy per institutional standards. After a minimum 72-day gap from the end of immunotherapy, patients undergo liver transplant. Primary outcome is a binary endpoint, and it will be assessed in patients undergoing liver transplant. Historically, 10-20% of patients are expected to experience acute cellular rejection within 30 days of transplant. We propose that an observed proportion of 20% treatment failure will be a clear indicator of safety in this pilot study, whereas an observed proportion of 50% failure will be a clear indicator of failure. Using these guardrails, with at least 20 patients going to transplant, we will have 80.6% power to demonstrate a failure proportion of 20% (4 patients experiencing failure) versus a null of 50% (10 patients experiencing failure), with a one-sided alpha of 0.05. With 25 patients going to transplant, the power will increase to 86% (other parameters being the same). Clinical trial information: NCT05027425 .